IMRT: State of the Art

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Radiation therapy is reaching new heights with IMRT. Addressing one of the major problems of conventional treatments, IMRT can deliver lethal dosages of radiation to tumors while sparing adjacent, critical structures. This means higher cure rates for patients, less complications and the ability to lead a more normal life during treatment. Radiation oncology professionals are leveraging the power of IMRT; treating brain, head and neck and prostate tumors, and exploring treatment for tumors of the kidney, breast, pancreas, lung, spine and cervix.

Intensity modulated radiation therapy (IMRT), an extension of conformal therapy, is highly precise, high-dose radiation therapy that targets cancer cells, while minimizing the exposure of nearby healthy tissue. The treatment option employs powerful inverse planning software to plan a precise dose of radiation in three dimensions, based on individual tumor size, shape and location. The delivery system then directs radiation at the tumor and modulates the intensity of pencil-thin beams of radiation with laser accuracy.

The combination of computer power and linear accelerator (linac) results in exquisite dose painting, says Richard Stark, director of Varian Medical Systems' delivery systems product line. "If you can deliver the dose very, very precisely, then you have the opportunity to reduce rates by reducing the dose to surrounding critical structures," he continues. "You also can increase the dose to your target volume without increasing the side effects."

Take, for example, IMRT as a treatment option for localized prostate cancer. It provides a higher radiation dosage to the prostate gland, while reducing the dosage reaching the rectum and bladder, potentially minimizing painful physical side effects.

"Prostate and head and neck cancer were the very first thing people attacked with IMRT," explains Stark. "What we are seeing in the literature is that it is being used in more and more places. You can use it in the lung. You can use IMRT for treatment of the pelvis, such as for cervical cancer." The University of Chicago Hospitals, one of the first medical centers to start treating gynecologic cancers in 1999 with IMRT, has treated more than 150 patients, according to Arno Mundt, MD, associate professor of radiation and cellular oncology at the University of Chicago and University of Illinois.

Jack Yang, PhD, chief medical physicist, radiation oncology, at the 527-bed Monmouth Medical Center in Long Branch, N.J., part of the Saint Barnabas Health Care System, says the radiation oncology department treats a lot of head and neck cancers with IMRT. Patients have experienced less side effects. "We spare the parotid gland and the patient is able to carry on the same function as they had before," explains Yang. "In the past, one of the side effects for radiation treatment has been destruction of the parotid glands and the patient will have a dry mouth symptom for life."

Yang emphasizes that IMRT opens the door for re-treatment. "Some patients who go through radiation treatment reach a tolerance on certain critical structures," says Yang. "The tumor may come back. What can you do? In the past, we could not do anything. With IMRT, we can take care of the tumor without overdosing the critical structure."


THE LEARNING CURVE

The therapeutic success of IMRT has fueled widespread adoption. In the United States, radiation oncology departments and free-standing cancer treatment centers are realizing that state of the art means IMRT. At the same time, the technology does not replace conventional radiotherapy methods - it is typically used to treat 30 to 40 percent of cancer patients.

One of the reasons boils down to what has been dubbed an obvious drawback of IMRT - the arduous nature of the technology. Since it is time-intensive, physicians will use IMRT when they want to control the dose from hitting critical structures or to treat tumors that are unreachable otherwise. Successful IMRT also requires a well-trained and large staff that includes radiation oncologists, medical physicists, dosimetrists and radiation therapists - positions which are often hard to recruit and keep filled.

The standard for IMRT planning requires CT scanning for image-based calculations and treatment. Planning software now provides fusion capability and radiation oncologists may spend a little more time overlaying CT scans with MRI or PET data to better define the target volume. Once the physician chooses the dose most appropriate for the tumor (and the dose acceptable for surrounding structures), a technique called inverse planning is used by the computer to decide the radiation delivered at every point. Once complete, medical physicists and dosimetrists also record and verify the planned treatment, as well as perform quality assurance. The physics alone can take three hours to three days to complete.

And experts agree that there is a steep learning curve involved. "When the learning curve goes away, the planning time is less," says Tim Fox, PhD, director of the division of medical physics, radiation oncology, at Emory University Hospital. "But it still takes a finite amount of time, depending on the site and the technique being used." Fox adds that some people can spend eight hours on a case. "The question is when do you finally end," he poses. "Part of the issue is that it is hard to judge if it's the best possible plan. The ideal prescription would be 100 percent of the dose to the tumor volume and zero dose everywhere else. So when you can't achieve that, because it's impossible, it's sometimes difficult to decide how much work you should put into it."

Facilities utilizing IMRT will eventually reduce turnaround time. Employing eight medical physicists, 12 dosimetrists and 15 radiation oncologists, Cancer Therapy Research Center (CTRC) in San Antonio, Texas, treats 45 to 65 patients daily on Nomos Corp.'s Peacock systems (now Nomos Radiation Oncology Division of North American Scientific Inc. after its acquisition in May).

Physicians and scientists at CTRC have conducted more than 120,000 IMRT procedures since 1997. According to Bill Salter, PhD, associate director of medical physics at CTRC, the most common cancers treated are prostate and head and neck. "IMRT has moved beyond infancy and moved into adolescence," opines Salter. "We are starting to see that more centers have IMRT than don't."

Salter hallmarks new treatment possibilities with IMRT, such as stereotactic body radiation therapy (SBRT). "Basically, it is the idea of taking radiosurgery - which is big doses of radiation that we have traditionally done in the brain - and taking them outside to body regions of the lung and liver," says Salter. "We have started to offer hope to patients who we really did not have much to offer before."


LIVING UP TO ITS PROMISE

IMRT research has proven better cure rates with less toxicity. Reimbursement for the technology was approved in 2001 by the Centers for Medicare and Medicaid Services. Both have influenced IMRT installation numbers over the past couple of years. According to a 2003 edition of the Radiation Oncology Census Database published by IMV Medical Information Division, IMRT is now provided at 38 percent of all radiation oncology facilities in the United States, up from 4 percent in 1998.

IMV data also indicate that capital budgets for radiation therapy equipment are increasing, with the average 2004 capital equipment budget estimated at $980,000, up 34 percent from 2003 budgets. Sites having budgets of $1.5 million or more have increased from 9 percent of sites in 1996 to 18 percent of sites with 2004 budgets.

This is significant since adding an IMRT program is a costly financial endeavor. Necessary equipment includes a linear accelerator (linac) with a multileaf collimator (MLC), treatment planning software, simulation devices and software, an adjustable patient couch and quality assurance components (plus a highly trained staff).

The good news is there are options; market penetration has fueled market competition and radiotherapy companies today offer a range of IMRT equipment. Nomos was the first company to commercialize IMRT in 1994. Varian and Elekta Inc. joined shortly thereafter and offer comprehensive IMRT delivery and treatment planning packages. Siemens used to be just an IMRT treatment delivery company until it acquired the radiation therapy business of MRC Systems GmbH - and its flagship KonRad Radiation treatment (RTP) software - in July 2003. Philips Medical Systems, which partners with RaySearch Laboratories of Stockholm, Sweden, offers IMRT treatment planning components. Its flagship radiation therapy planning system includes Pinnacle3.

"An oncology clinic can install a brand new linac that is capable of doing IMRT or update with hardware and software a linear accelerator that may have been previously installed, but is not equipped to do IMRT," says Jim Bilich, product manager for Siemens' oncology division.

A new linear accelerator can cost $1 million to $2 million. Upgrading an existing system can be less expensive, more in the $500,000 to $800,000 range. However, Bilich says there is much to consider, such as the add-on MLC, necessary software, inverse planning software, quality assurance, 3D simulation and information systems upgrades.

"If you do upgrade your linac, there are also upgrades you have to do to your information system to support a new MLC, to support automated field sequencing and typically to support a sequence of fields being delivered," explains Bilich.

What about downtime? Installing a new linac or upgrading an existing one disrupts clinical activity. Atlanta Oncology Associates (AOA) runs seven free standing radiation oncology clinics in Georgia and is in the process of replacing 11-year-old linacs with Elekta's PreciseBeam IMRT systems. Careful planning and diligence on behalf of the project team minimized downtime. Its Alpharetta treatment site recently installed a Precise Treatment system and reported a total downtime of less than six weeks. "That included taking out the old machine, prepping the room for the new machine, installing the new machine, acceptance testing and training of the people," says Peter Mondolak, PhD, director of physics for Atlanta Oncology Associates.


SEEING IS BELIEVING

Looking into the future, experts say more research will be published examining the long-term side effects of IMRT. Chicago's Mundt examines the possibility of second malignancies as a result of IMRT. "We cut back on the normal high doses to normal tissues [with IMRT], but you have to take into consideration that the dose will go somewhere," says Mundt. "This low dose may spread to other tissues that might not have gotten much dose [in the past]. There are some questions about the long-term risk of that. This is the point in time where we should start seeing if there is a significant second malignancy rate. We haven't yet, but it does not mean if we wait another 10 years it won't be there."

Emory's Fox opines that the future for IMRT also may entail a little bit of forward planning. "People are starting to look at forward planning where the dosimetrist or physicist create stepped fields instead of just letting the computer do the planning," explains Fox. "Forward planning seems to be one of the things a lot of vendors are starting to offer."

The most talked-about future advancement for IMRT is the inclusion of image- guided radiation therapy (IGRT). Image guidance will help radiotherapy play a bigger role in cancer management because the added precision will reassure caregivers that the radiation is being administered to the same spot, despite organ motion.

"Radiotherapy, when you compare it to surgery or chemotherapy, tends to be the poor step child," says Varian's Stark. "Referrals very often go to surgery and chemotherapy first. I think radiotherapy is going to play a more dominant role in cancer management by being able to treat more cancers. The way it is going to be able to do that is to be able to further increase the dose we give while avoiding more normal tissue. IMRT took us in a big step in that direction, but now we need image guidance to take us the extra step."